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Global Translational Medicine





                                        ORIGINAL RESEARCH ARTICLE
                                        Optimization of gelatin-based cell carriers for

                                        tooth-germ organoids



                                        Anisha Jackson , Cemile Bektas , and Yong Mao*
                                        Laboratory for Biomaterials Research, Department of Chemistry and Chemical Biology, Rutgers
                                        University, Piscataway, New Jersey, United States of America
                                        (This article belongs to the Special Issue: Soft and Hard Tissues Reconstruction in Dentistry)



                                        Abstract

                                        Tooth  loss  is  a  widespread  condition  that  significantly  impacts  quality of life,  and
                                        effective functional treatments remain limited. Research in regenerative technologies
                                        is advancing toward solutions that are functional, customizable, and biologically
                                        integrative.  Tooth-germ  organoids  –  three-dimensional  constructs  cultured  in vitro
                                        – hold promise for developing functional dental tissues. Hydrogel microparticles,
                                        selected for their structural support, resemblance to the natural extracellular matrix, and
                                        moldability, serve as carriers and scaffolds for organoid culture. Methacrylate gelatin
                                        microspheres (GelMA MS) have previously been identified as suitable scaffolds for dental
                                        organoids, as they support the composition of multiple cell types necessary for forming
                                        functional dental tissue. However, producing GelMA MS at a scale sufficient for tooth-
            *Corresponding author:      organoid  research  is  time-consuming  and  suffers  from  limited  reproducibility.  This
            Yong Mao
            (maoy@dls.rutgers.edu)      study aims to develop alternative gelatin-based carriers with simpler, more reproducible
                                        fabrication processes that provide equal or enhanced support for tooth-germ organoid
            Citation: Jackson A, Bektas C,   formation. Two alternative carriers – gelatin microspheres (Gel MS) and micronized
            Mao Y. Optimization of gelatin-
            based cell carriers for tooth-germ   photo-crosslinked GelMA microparticles (GelMA MP) – were evaluated in comparison
            organoids. Global Transl Med.   to GelMA MS and GelMA hydrogel. Both Gel MS and GelMA MP were found to be more
            2025:4(1):67-79.            cost-effective, easier to produce, and more reproducible than GelMA MS. To assess their
            doi: 10.36922/gtm.5897
                                        effectiveness as cell carriers, the growth and osteogenic differentiation of human dental
            Received: November 13, 2024  pulp stem cells (hDPSCs) were directly compared across all carriers. Results showed that
            1st revised: December 11, 2024  hDPSCs demonstrated significant proliferation and formed organoid-like clusters on
                                        both Gel MS and GelMA MP, similar to GelMA MS. Cell viability was higher on GelMA MS,
            2nd revised: December 24, 2024
                                        GelMA MP, and Gel MS than in GelMA hydrogel, a commonly used cell carrier. Among
            Accepted: December 25, 2024  the four cell carriers, Gel MS provided the best support for the growth and osteogenic
            Published online: January 16,   differentiation of hDPSCs. This study identifies viable alternatives to GelMA MS and
            2025                        highlights the superior performance of Gel MS as a cell carrier, advancing tooth-germ
            Copyright: © 2025 Author(s).   organoid research and developing potential therapeutic applications.
            This is an Open-Access article
            distributed under the terms of the
            Creative Commons Attribution   Keywords: Gelatin microspheres; Methacrylate gelatin; Microparticles; Tooth; Organoids;
            License, permitting distribution,   Stem cells; Cell-carriers
            and reproduction in any medium,
            provided the original work is
            properly cited.
            Publisher’s Note: AccScience
            Publishing remains neutral with   1. Introduction
            regard to jurisdictional claims in
            published maps and institutional   Dental interventions can partially restore tooth functionality, but the ultimate goal of
                                                                                                      1
            affiliations.               dental repair is the regeneration of natural teeth and associated dental tissues.  Among


            Volume 4 Issue 1 (2025)                         67                              doi: 10.36922/gtm.5897
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